In short
TIL cells (tumor-infiltrating lymphocytes) are immune cells taken from a person’s tumor, grown and prepared in a lab, and then given back by infusion to help the immune system fight cancer. Several clinical trials are studying TIL-based treatments in different cancers, including advanced solid tumors, metastatic melanoma, and stage III/IV ovarian cancer. These studies mainly look at safety (side effects) and how well the treatment may control or shrink tumors.
Key points
- TIL cells are a type of cell therapy where immune cells from a tumor are prepared in a lab and then infused back into the patient. Clinical trials are testing TIL approaches in advanced solid tumors, metastatic melanoma, and stage III/IV ovarian cancer. The main focus is safety, using standard side-effect grading systems (CTCAE). Researchers also track whether tumors shrink or stay controlled using imaging rules like RECIST v1.1, and they measure outcomes such as progression-free survival and overall survival. Some studies combine TIL therapy with other immune treatments, including nivolumab, low-dose peginterferon alfa, or low-dose IL‑2. These trials also collect immune data to understand which immune signals may link to better responses.
At a glance
- Drug/therapy studied
- TIL cells (tumor-infiltrating lymphocytes), including Meta10-TIL (metabolically armed TIL)
- Cancers studied
- Advanced solid tumors; metastatic melanoma; stage III/IV epithelial high-grade ovarian/fallopian tube/primary peritoneal cancer
- How TIL therapy is given
- Intravenous infusion; one trial uses lymphodepletion chemotherapy (cyclophosphamide + fludarabine) before infusion
- Combination approaches
- TIL + nivolumab; TIL + low-dose PEG‑IFNα + nivolumab; adoptive T cell therapy + low-dose IL‑2
- Main safety measurement
- Adverse events graded with CTCAE (v4.0 or v5.0), including dose-limiting toxicities in dose-finding work
- Main effectiveness measurements
- ORR, DOR, PFS, OS, disease control rate; responses assessed by RECIST v1.1 (and sometimes irRC)
- Follow-up time mentioned
- Up to 1 year post infusion in the advanced solid tumor Meta10-TIL trial
- Extra research questions
- Immune monitoring, biomarker profiles, and correlations between immune markers and clinical response
What are TIL cells?
TIL cells stands for tumor-infiltrating lymphocytes. These are immune cells, mainly T-cells, that are already inside a person’s tumor. The idea behind TIL therapy is to use these tumor-fighting cells as a treatment.
In the trials provided, TIL cells are described as a cell therapy product given by intravenous infusion (through a vein). One investigational version is called Meta10-TIL, described as “metabolically armed” TIL therapy for people with advanced solid tumors.
Which clinical trials and cancers are being studied?
The provided trial data includes TIL-based approaches in several cancer settings:
- Advanced solid tumors: An open-label study evaluates the safety and signs of benefit of Meta10-TIL therapy in advanced solid tumors.
- Metastatic melanoma: A phase I/II, single-center study (ACTME) evaluates TIL therapy together with nivolumab, and later the combination of TIL plus low-dose PEG-IFNα plus nivolumab, for progressive unresectable stage III or stage IV melanoma.
- Ovarian carcinoma: A phase I/II trial (OVACURE-2) studies adoptive T cell therapy (using TIL cells) plus low-dose IL-2 as a first-line neoadjuvant strategy in stage III/IV epithelial high-grade ovarian, fallopian tube, or primary peritoneal cancer.
How TIL therapy is given in these studies
Across the trials, the TIL product is given as an infusion into a vein.
- Meta10-TIL for advanced solid tumors: Participants receive nonmyeloablative lymphodepletion chemotherapy (a pre-treatment that reduces immune cells without fully wiping out bone marrow function) with cyclophosphamide and fludarabine, followed by Meta10-TIL infusion on day 0.
- ACTME in metastatic melanoma: The study evaluates safety and toxicity of TIL and nivolumab first, and later the combination of TIL, PEG‑IFNα, and nivolumab.
- OVACURE-2 in ovarian cancer: The study evaluates TIL-based adoptive T cell therapy plus low-dose IL-2, and aims to determine dosing for phase II based on dose-limiting toxicities (DLTs).
What outcomes are measured (safety and effectiveness)
Safety outcomes
A central goal in these studies is to understand side effects. Trials measure adverse events (AEs) and grade them with CTCAE (a standard scale for severity).
- In the Meta10-TIL advanced solid tumor study, the primary outcome is adverse events graded by NCI CTCAE v5.0 over 1 year after infusion.
- In ACTME metastatic melanoma, safety and toxicity are evaluated using CTCAE 4.0, and certain grade 3 toxicities and serious adverse events may be considered acceptable if they do not lead to stopping treatment.
- In OVACURE-2 ovarian cancer, toxicity related to TIL plus low-dose IL-2 is assessed using NCI CTCAE v5.0, with a focus on grade greater than III and identifying DLTs to help choose a recommended dose for phase II.
Effectiveness outcomes
These trials also look for signs the treatment may control cancer. Common measures include:
- Objective response rate (ORR): The percent of patients with a confirmed partial response (PR) or complete response (CR), often measured with RECIST v1.1.
- Duration of response (DOR): How long a PR or CR lasts before the cancer grows or the patient dies.
- Progression-free survival (PFS): Time until the cancer progresses or death occurs.
- Overall survival (OS): Time from a defined study point (for example, infusion date) to death.
- Disease control rate (DCR): Percent of patients with CR, PR, or stable disease (SD).
In the ACTME melanoma study, disease control is assessed with imaging such as CT and/or MRI using RECIST 1.1 and also immune-related response criteria (irRC), which are sometimes used in immunotherapy research to better capture immune-related patterns of tumor change.
Who may join these trials (common inclusion and exclusion themes)
Each study has its own detailed rules. From the provided trial text, common themes include confirming the cancer type and stage, showing the cancer can be measured (or tracked) in standard ways, and making sure general health is strong enough for intensive immunotherapy approaches.
Examples of inclusion requirements described in the provided trials
- Confirmed diagnosis and stage (for example, metastatic melanoma stage III unresectable or stage IV; or epithelial high-grade ovarian/fallopian tube/primary peritoneal cancer stage III/IV).
- Measurable disease using RECIST v1.1 (some ovarian cancer participants may also qualify via elevated CA125 criteria as described).
- Functional status requirements such as WHO performance status ≤ 1 or ECOG performance status 0–1, meaning the person is fairly active and able to care for themselves.
- Laboratory values in acceptable ranges (blood counts and organ function measures), and negative viral testing for infections such as HIV, hepatitis B, and hepatitis C as specified.
Examples of exclusion considerations described in the provided trials
- Pregnancy or breastfeeding.
- Some forms of serious heart disease, such as NYHA Class III or IV.
- Active serious infections requiring antibiotics.
- Active immunodeficiency or autoimmune disease requiring immune-suppressing drugs (with vitiligo specifically noted as not excluding participation in these trials).
- Brain metastases limitations differ by study: the melanoma trial allows brain metastases only if neurologically stable for at least 2 months and without dexamethasone; the ovarian trial excludes brain metastases.
Immune tests and biomarkers studied
Beyond tumor measurements and side effects, some trials include detailed immune research to understand why some patients respond better than others.
- The metastatic melanoma ACTME trial includes goals such as building a possible biomarker profile, comparing immune features in patients with and without response, and studying the infused T cell product using immunomonitoring. It also describes evaluating immune characteristics in PBMCs (blood immune cells) and exploring differences between CD8-rich and CD8-poor metastases, including using CD8-immunoPET/CT methods as described in the trial record.
- The ovarian cancer OVACURE-2 trial lists secondary objectives including immune monitoring with TCR clonotypes and tracking immune cell subsets such as CD8/CD4 and other immune cell categories named in the protocol summary.
- The Meta10-TIL advanced solid tumor trial includes plans to characterize pharmacokinetic (PK) and pharmacodynamic (PD) profiles, which broadly means tracking the therapy in the body over time and its biological effects.